Orally Bioavailable Quinoxaline Inhibitors of 15-Prostaglandin Dehydrogenase (15-PGDH) Promote Tissue Repair and Regeneration

J Med Chem. 2022 Nov 24;65(22):15327-15343. doi: 10.1021/acs.jmedchem.2c01299. Epub 2022 Nov 2.

Abstract

15-Prostaglandin dehydrogenase (15-PGDH) regulates the concentration of prostaglandin E2 in vivo. Inhibitors of 15-PGDH elevate PGE2 levels and promote tissue repair and regeneration. Here, we describe a novel class of quinoxaline amides that show potent inhibition of 15-PGDH, good oral bioavailability, and protective activity in mouse models of ulcerative colitis and recovery from bone marrow transplantation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis, Ulcerative / drug therapy
  • Dinoprostone
  • Hydroxyprostaglandin Dehydrogenases* / antagonists & inhibitors
  • Mice
  • Quinoxalines* / pharmacology

Substances

  • 15-hydroxyprostaglandin dehydrogenase
  • Dinoprostone
  • Hydroxyprostaglandin Dehydrogenases
  • Quinoxalines